Silva, Nicola (2009) Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability. [Tesi di dottorato] (Inedito)
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Functional characterization of the Caenorhabditis elegans gene fcd-2 during meiosis and in maintenance of genomic stability |
| Autori: | Autore Email Silva, Nicola nicola.silva78@gmail.com |
| Data: | 27 Novembre 2009 |
| Numero di pagine: | 76 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Istituzioni (extra): | CNR. Istituto di Genetica e Biofisica "Adriano Buzzati-Traverso" |
| Dipartimento: | Biochimica e biotecnologie mediche |
| Scuola di dottorato: | Medicina molecolare |
| Dottorato: | Genetica e medicina molecolare |
| Ciclo di dottorato: | 22 |
| Coordinatore del Corso di dottorato: | nome email Di Lauro, Roberto dilauro@szn.it |
| Tutor: | nome email La Mantia, Girolama lamantia@unina.it |
| Data: | 27 Novembre 2009 |
| Numero di pagine: | 76 |
| Parole chiave: | Fanconi anemia, genomic stability, C. elegans |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/18 - Genetica |
| Depositato il: | 19 Mag 2010 13:51 |
| Ultima modifica: | 21 Gen 2015 11:34 |
| URI: | http://www.fedoa.unina.it/id/eprint/3822 |
| DOI: | 10.6092/UNINA/FEDOA/3822 |
Abstract
Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with defects in the repair of DNA interstrand cross-links (ICLs) resulting in occasional developmental defects and in ICL hypersensitivity of patient cells, yet the precise role of the FA proteins during DNA repair has remained unclear. I will present evidence that FA counteracts illegitimate repair of DNA lesions by non-homologous end joining (NHEJ). FCD-2 has proven to be involved in the choice of repair pathways: 1) fcd-2 mutants show an increase in spo-11 dependent RAD-51 foci and in germline apoptosis, 2) in genetic backgrounds where chiasma formation is abrogated (such as msh-4 and syp-2) resolves in less than the expected 12 DAPI stained bodies at diakinesis, such bodies are the results of chromosome fusions also involving non-homologous chromosomes (as demonstrated by FISH), 4) in the contemporary absence of FCD-2 protein, crossovers and NHEJ (i.e. in the triple mutants fcd-2; syp-2;lig-4 and fcd-2; msh-4;lig-4) we observe more than 12 DAPI stained bodies at diakinesis, a phenotype reminiscent of what observed in brc-1;syp-2 and brc-1;msh-4 double mutants (brc-1 being the ortholog of human BRCA1, see Adamo et al. 2008 enclosed). Furthermore, other fcd-2 mutant phenotypes such as interstrand cross-linking sensitivity and hypermutation are due to promiscuous use of NHEJ.
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